Neurotherapeutic Potential of Photobiomodulation in a 3D Model of Alzheimer's Disease Induced by Oxidative Stress

Purpose Alzheimer’s disease (AD) is a progressive neurodegenerative condition that, despite its high global incidence, still lacks effective treatments capable of altering its course. Therefore, this study aimed to investigate the neuroprotective and neurorestorative effects of photobiomodulation (PBM, 660 nm) in a three-dimensional (3D) neuronal model of AD induced by oxidative stress. We sought to determine whether PBM could attenuate cellular damage, reduce oxidative imbalance, and preserve neuronal morphology under AD-like conditions. Methods A previously validated 3D neuronal model of AD, based on differentiated SH-SY5Y spheroids stressed with H₂O₂ (200 µM, 1 h), was used. Spheroids were assigned to four experimental groups (Control, PBM, H₂O₂, H₂O₂+PBM). PBM was performed by 660 nm LED irradiation (3 J/cm²). Cell viability, intracellular reactive oxygen species (ROS) levels, and neuronal morphology were assessed. Results PBM increased cell viability in both control and H₂O₂-exposed spheroids, with partial recovery of metabolic activity following oxidative injury. Intracellular ROS levels were significantly reduced by PBM, indicating attenuation of the oxidative imbalance. Morphological evaluation showed partial preservation of neuronal architecture, with PBM reducing nuclear and structural disruptions characteristic of oxidative stress. Conclusion PBM attenuated oxidative damage in a 3D model of AD, by increasing cell viability, reducing intracellular ROS, and partially preserving neuronal morphology. These findings support PBM as a promising adjuvant therapeutic approach for neurodegenerative conditions and reinforce the relevance of 3D neuronal spheroids as a platform for in vitro AD research.